Table 3.

Hepatic microenvironment related therapeutic implications in breast cancer liver metastasis.

Hepatic micoenvironment cells	Related moleculars or pathway	Therapeutic implications	References
Breast cancer stem cells	CD44, TGF-β1 pathway	bivatuzumab mertansine	(68, 69, 145)
Hepatocytes	Claudin-2, ECM components (such as fibronectin and type IV collagen), integrin complexes	Lyn-selective kinase inhibitor Bafetinib (INNO-406)	(52, 79–81)
	E-cadherin, ERK pathway	ROS1 inhibitors (crizotinib)	(82, 146, 147)
Macrophages	STAT6, IL-4 and IL-13, CD47	PLD inhibitors [FIPI (dual PLD1/PLD2 inhibitor) or VU0155072-2 (PLD2 inhibitor)], cabazitaxel	(58, 86, 148, 149)
NK cells	Interleukin-15, interferon-γ, CXCL12 and CXCR4	Interleukin-15 based immunotherapy	(94)
Neutrophils	G-CSF, P53, WNT, KIAA1199, TGFβ-CXCL3/1-CXCR2 axis	LGK974 (a Porcupine inhibitor blocking acylation of Wnt), KIAA1199 inhibitors	(97, 98, 150–152)

ECM, Extracellular matrix; PLD, Phospholipase D; NK cells, Natural killer cells; TGF-β, Transforming growth factor-β; ERK, Extracellular regulated protein kinases; IL, Interleukin; STAT, Signal transducer and activator of transcription; CXCL, Chemokine (C-X-C Motif) ligand; CXCR, Chemokine (C-X-C motif) receptor; G-CSF, Granulocyte colony stimulating factor. Figure legends.